Prevalence and molecular analysis of two hot spots for ectopic recombination leading to XX maleness.

Two hot spots of ectopic Xp-Yp recombination have previously been shown to be at the origin of XX maleness (Weil et al., 1994, Nature Genet. 7:414-419). To get more insight into the molecular basis of the abnormal interchange, 25 Y(+) class 3 XX male patients were studied. The two hot spots were found to account for the aberrant exchange in more than 50% of the cases. In addition, there is a correlation between the prevalence of each hot spot and the degree of X-Y homology between the corresponding fragments. Sequencing of the X-Y junctions in six patients, who carried a breakpoint mapping in either of these two hot spot fragments, showed that their precise locations were different from one individual to the other. In particular, the results obtained here in four new patients exclude the possibility that the repeated elements, present in these X-Y homologous fragments, are responsible for the high incidence of X-Y interchanges observed. Moreover, the breakpoints of all 25 class 3 XX males were found to be arranged in the same order on the X and Y chromosomes. This suggests that most ectopic recombinations leading to class 3 XX maleness involve X-Y homologous sequences persisting from an ancestral larger block of homology on the short arms of both sex chromosomes.